Synergistic Integration of Twin-Screw Hot-Melt Granulation and Selective Laser Melting for High-Dose Extended-Release 3D-Printed Tablets

Powder-based 3D printing techniques such as selective laser sintering (SLS) are constrained by incomplete particle fusion and high porosity, limiting their utility for high-dose, extended-release pharmaceutical dosage forms. Here, we report a synergistic manufacturing strategy that couples twin-screw hot-melt granulation (HMG) with selective laser melting (SLM) to overcome these structural limitations. Using acetaminophen (ACM) as a highly soluble model drug and glyceryl behenate (Compritol® 888 ATO) as the binder, twin-screw HMG was utilized to prepare flowable, lipid-based feedstock granules. Lipid concentration and HMG process parameters, namely screw speed and temperature profile, were optimized to achieve ideal micromeritic properties that facilitated uniform powder bed packing for SLM, without altering the drug or lipid crystallinity. The SLM-printed tablets showed high mechanical strength (up to 224.8 N) and density, indicating complete particle fusion. Lipid content showed an inverse effect on the drug release rate, with the F-75 formulation (25% C-888) reaching a cumulative release of 44.8% after 24 hours. X-ray micro-computed tomography (μ-CT) confirmed a dense internal structure and a dynamic, surface-driven dissolution process characterized by boundary erosion, which was highly consistent with the Korsmeyer-Peppas kinetic model (R 2 ≥ 0.98). Overall, this synergistic HMG-SLM proof-of-concept approach demonstrates the feasibility of utilizing hydrophobic, low-melting-point lipid matrices to fabricate high-dose, extended-release 3D-printed dosage forms.